A Phase 1 Double-Blind, Double-Dummy, Parallel-Group, Randomized, Positive Control Study Using fMRI to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users

The main purpose of this study is to evaluate the effect of NKTR-181 on brain activity in healthy, non-physically dependent recreational opioid users. This study will last about 88 days for each participant.

开始日期2018-10-22

申办/合作机构

Nektar Therapeutics

NCT02367820

/ Completed临床3期

A Phase 3 Multicenter, Open-Label, 52-Week Study To Evaluate the Long-Term Safety and Tolerability of NKTR-181 in Subjects With Moderate to Severe Chronic Low Back Pain or Chronic Non-Cancer Pain

The purpose of this 52-week open label study is to determine the long-term safety of a new opioid molecule, NKTR-181, in patients with moderate to severe chronic low back pain or chronic non-cancer pain.

开始日期2015-04-14

申办/合作机构

Nektar Therapeutics

NCT02362672

/ Completed临床3期

A Phase 3 Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of NKTR-181 in Opioid-Naive Subjects With Moderate to Severe Chronic Low Back Pain

The purpose of this study is to determine whether a new opioid molecule, NKTR-181, is effective for the relief of moderate to severe chronic low back pain as compared to a placebo.

开始日期2015-03-11

申办/合作机构

Nektar Therapeutics

100 项与 Loxicodegol 相关的临床结果

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100 项与 Loxicodegol 相关的转化医学

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100 项与 Loxicodegol 相关的专利（医药）

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项与 Loxicodegol 相关的文献（医药）

2021-07-01·Cellular and molecular neurobiology3区 · 医学

Preclinical Assessment of the Analgesic Pharmacology of NKTR-181 in Rodents

3区 · 医学

Article

作者: Liu, Yi ; Schmidt, William K ; Yang, Miao ; Swiokla, Juliana ; Navratilova, Edita ; Miyazaki, Takahiro ; Zalevsky, Jonathan ; Porreca, Frank ; Kopruszinski, Caroline M ; Lee, Yeon Sun ; VanderVeen, Laurie

OBJECTIVE:

Pharmacological evaluation of the mu-opioid receptor (MOR) agonist properties of NKTR-181 in rodent models.

METHODS:

Graded noxious stimulus intensities were used in rats to establish the antinociceptive potency and efficacy of NKTR-181 relative to morphine, fentanyl, and oxycodone. Characteristics of MOR agonist actions, as measured by antinociceptive tolerance and cross-tolerance, as well as opioid-induced hyperalgesia (OIH) and naloxone-precipitated withdrawal in NKTR-181- and morphine-dependent in mice, were compared.

RESULTS:

NKTR-181 showed dose- and time-related antinociception with similar maximal effects to morphine in the rat and mouse hot-water tail-flick test. No sex or species differences were observed in NKTR-181 or morphine antinociception. Rats treated with NKTR-181 and morphine exhibited decreases in both potency and maximal efficacy as nociceptive stimulus intensity was increased from a water temperature of 50 °C to 54 °C. Evaluation of antinociception at a high stimulus intensity revealed that oxycodone and fentanyl exhibited greater efficacy than either NKTR-181 or morphine. The relative potency difference between NKTR-181 and morphine across all tail-flick studies was determined to be 7.6-fold (90% confidence interval, 2.6, 21.5). The peak antinociceptive effect of NKTR-181 was delayed compared to that of the other opioids and cumulative drug effects were not observed. Repeated treatment with escalating, approximately equi-analgesic doses of NKTR-181 or morphine, produced antinociceptive tolerance and cross-tolerance. Under these pharmacological conditions, OIH and naloxone-precipitated physical dependence were similar for NKTR-181 and morphine.

CONCLUSIONS:

NKTR-181 had a slower onset, but similar efficacy, to morphine in the models studied supporting reduced abuse potential while maintaining analgesic effect in comparison with current opioids.

2020-08-01·Pain medicine (Malden, Mass.)3区 · 医学

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain

3区 · 医学

Article

作者: Siddhanti, Suresh ; Gudin, Jeffrey ; Gimbel, Joseph ; Henningfield, Jack E ; Schnoll, Sidney ; Lu, Lin ; Tagliaferri, Mary ; Doberstein, Stephen K ; Di Fonzo, Carlo ; Rauck, Richard ; Katz, Nathaniel

Abstract:

Objective:

To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist.

Design:

Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP).

Setting:

Conducted in the United States at multiple sites.

Methods:

SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5 mg/acetaminophen 300 mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0 gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events.

Results:

Of 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N = 309, NKTR-181; N = 301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ≥13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ≤2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible “withdrawal” events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo).

Conclusions:

NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.

2020-07-01·Pain medicine (Malden, Mass.)3区 · 医学

Long-term Safety and Tolerability of NKTR-181 in Patients with Moderate to Severe Chronic Low Back Pain or Chronic Noncancer Pain: A Phase 3 Multicenter, Open-Label, 52-Week Study (SUMMIT-08 LTS)

3区 · 医学

Article

作者: Gimbel, Joseph ; Argoff, Charles ; Rauck, Richard ; Doberstein, Stephen K ; Tagliaferri, Mary ; Tagliaferri, Margit ; Hale, Martin ; Siddhanti, Suresh ; Gudin, Jeffrey ; Katz, Nathaniel ; Markman, John ; Lu, Lin ; Potts, Jeffrey ; Wild, James ; Agaiby, Eva

Abstract:

Objective:

To evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP).

Design:

Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (∼14 days after the last dose of NKTR-181).

Setting:

Multicenter, long-term clinical research study.

Methods:

NKTR-181 administered at doses of 100–600 mg twice daily (BID) was evaluated in opioid-naïve and opioid-experienced patients. Patients were enrolled de novo or following completion of the randomized, placebo-controlled phase 3 efficacy study (SUMMIT-07). Safety assessments included adverse event documentation, measurements of opioid withdrawal, and clinical laboratory tests. Effectiveness was assessed using the modified Brief Pain Inventory Short Form (mBPI-SF).

Results:

The study enrolled 638 patients. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (26%) and nausea (12%). Serious TEAEs, reported in 5% of patients, were deemed by investigators to be unrelated to NKTR-181. There were no deaths or reported cases of respiratory depression. A sustained reduction in mBPI-SF pain intensity and pain interference from baseline to study termination was observed throughout treatment. Only 2% of patients discontinued NKTR-181 due to lack of efficacy, and 11% discontinued due to treatment-related AEs. NKTR-181 doses of up to 600 mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events.

Conclusions:

The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.

项与 Loxicodegol 相关的新闻（医药）

2024-11-18

·CPHI制药在线

新型阿片类镇痛药物的研发进展

关注并星标CPHI制药在线阿片类镇痛药是目前已知疗效最好的镇痛药之一，然而其便秘、耐受和成瘾等毒副作用严重限制了其临床应用。近年来，随着对阿片受体信号转导机制的深入认知和药物设计技术的不断进步，研究者们尝试了许多有前景、不同于传统的改造吗啡骨架结构的全新方法，致力于开发低毒高效的阿片类镇痛药。 01 偏向型 μ 受体激动剂阿片类药物通过不同的细胞内信号途径产生不同的作用。研究发现，G蛋白偶联受体 (Gprotein-coupled receptor, GPCR)激活后，在其下游除了G蛋白依赖型通路外，还存在另一条由β-arrestin介导的信号通路，不同的配体可以不同程度地激活这两条通路，甚至只激活其中一条，这种现象称为“偏向性激活”。研究显示，G蛋白依赖型通路主要介导镇痛镇静，而β-arrestin 通路主要介导呼吸抑制、胃肠功能紊乱、药物耐受等。说明若某个阿片受体激动剂可以偏向性激动G蛋白信号通路，其镇痛疗效与毒副作用的平衡关系会更优，这为低毒高效阿片类镇痛新药的发现提供了理论基础。目前，丁丙诺啡、奥赛利定和PZM21 是比较有代表性的G蛋白偏向性激动剂。丁丙诺啡是由英国Reckitt Benckiser公司基于吗啡骨架所设计的，于 1978 年获批上市。该药不仅能够有效治疗急性和慢性疼痛，还可通过替代疗法减轻阿片类药物的成瘾性。丁丙诺啡的镇痛疗效媲美吗啡，但其呼吸抑制等不良反应的发生率较吗啡更低。奥赛利定，由美国 Trevena公司于2013 年研发。在细胞水平上，该药对G蛋白信号通路的激活能力与吗啡相近，但招募β-arrestin 2的能力远低于吗啡；在动物水平上，该药显示出略强于吗啡的镇痛效力，并且不易诱发呼吸抑制。2020年，奥赛利定获美国 FDA 批准上市，用于中重度急性疼痛的治疗，但该药仍会引发恶心、呕吐、便秘等不良反应。 PZM21是首个基于阿片受体晶体结构所设计的G蛋白偏向性激动剂。在细胞水平上，其偏向性与奥赛利定不相上下；在啮齿和灵长类动物水平上，其镇痛效力与吗啡、羟考酮相当且持续时间更久，并且没有成瘾性。但是，PZM21 仍未能避免便秘、耐药等不良反应。此外，引入苯并二氧戊环取代 PZM21 分子结构中的羟基，该衍生物可表现出比母体更强的镇痛活性和更大的G蛋白信号通路偏向性。有研究通过对配体-受体复合物冷冻电镜结构的解析和对比，发现 PZM21 和奥赛利定分别为完全不激活和部分激活 β-arrestin 信号通路，而芬太尼和吗啡则是强效激活β-arrestin 信号通路，这阐释了偏向性激动剂招募 β-arrestin 的结构细节，为开发低毒高效的偏向性阿片类镇痛药夯实了结构基础。近日，国内关于G蛋白偏向性阿片受体激动剂的临床研究取得重大突破。江苏恒瑞医药股份有限公司的泰吉利定（产品开发名为 SHR8554）是一种 μ 阿片受体的偏向性小分子激动剂，具有良好的镇痛作用、安全性和耐受性，于 2024 年 1 月 31 日获我国国家药品监督管理局批准上市，适用于腹部手术后的中重度疼痛，是国内首款自主研发的一类阿片类镇痛创新药。绿叶制药集团有限公司的G蛋白偏向性阿片受体激动剂 LPM-3480392 已先后在中国和美国完成了腹部手术中重度疼痛的Ⅱ期临床试验（CTR20222358、NCT06204120），关于骨科手术术后中重度疼痛的Ⅱ期临床试验（CTR20233389）正在有序开展中。 02 混合阿片受体激动剂以及 “一药多靶”策略多种药物联用的“鸡尾酒”疗法，在癌症、艾滋病和慢性疼痛等疾病治疗中均取得了良好成效。研发人员基于“鸡尾酒”疗法提出了“一药多靶”的多重药理学新理念，即作用于多个靶标的单一组分化合物，有助于平衡各靶标活性并产生协同作用。在痛觉相关的受体或信号通路中，μ阿片受体的调控效果最为显著。因此，阿片类“一药多靶”策略主要是围绕μ阿片受体开展的。根据靶标组合的不同，阿片类“一药多靶”药物主要分为下述两类。 ① 阿片受体家族不同亚型之间的组合，即：除靶向激动μ阿片受体以外，药物还作用于δ、κ 或 NOP 受体。研究发现，敲除 δ 受体可减轻 μ 受体激动剂的成瘾、耐受等副作用，以此为理论基础所设计的 μ 受体激动剂/δ 受体拮抗剂显示出更少的不良反应。有趣的是，μ/δ 受体双靶点激动剂同样显示出较好的镇痛潜力。此外，κ 和 NOP 受体也能够协同调节 μ 受体的生理效应。Cebranopadol 是一款极有代表性的“一药多靶”药物，由美国 Tris 公司开发。在细胞水平上，该药对多个阿片受体亚型都有较高的亲和力和激动活性（尤其是对μ和 NOP 受体），多靶点特性突出；在啮齿和灵长类动物水平上，该药的镇痛效力远高于吗啡，且不良反应更少。目前，该药在癌症疼痛、糖尿病周围神经病变、骨关节炎引发的慢性疼痛和药物滥用潜力评估等近10项临床试验中均取得了良好进展。 ② 阿片受体与非阿片受体的组合，除靶向激动μ阿片受体以外，药物还作用于非阿片系统的受体或信号通路，如神经肽FF（neuropeptide FF，NPFF）受体、神经激肽受体、胆囊收缩素受体等。以 NPFF 为例，有学者以阿片受体激动剂 morphiceptin 和 NPFF 类似物PFRTicNH2为母体设计了多靶点阿片肽药物 MCRT，该药显示出强效的镇痛活性和极少的不良反应；另有学者基于阿片受体激动剂和 NPFF 构建了 DN-9 等多个多靶点分子，其有效性和安全性均优于吗啡。在已上市的阿片类镇痛药中，具有“一药多靶”特性的药物占有很大比例，包括地佐辛和他喷他多等十余种药物都属于此类。相比吗啡等专一性 μ 阿片受体激动剂，多靶点阿片类镇痛药的安全性普遍较好。例如地佐辛，其呼吸抑制等不良反应的发生率非常低且有封顶效应，因而备受医患关注，占据了我国麻醉镇痛药市场约60% 的份额。多靶点药物的设计策略为安全高效的新型阿片类镇痛药的研发提供了更多可能性。 03 外周阿片受体激动剂众所周知，阿片受体在脑和脊髓之外的周围神经系统有着广泛的分布。透过血-脑屏障激活中枢神经系统的阿片受体，是阿片类药物发挥强效镇痛作用的关键，也是成瘾、过度镇静等副作用的根本原因。因此，“不上头”的外周阿片受体激动剂愈发受到关注。一种方法是研究本身不通过血脑屏障的药物，该研究集中于κ 受体激动剂，以asimadoline (EMD61753) 为代表，但 asimadoline 在镇痛方面表现差强人意，上市后主要用于肠易激综合征。再者，可采用纳米载体搭载阿片类药物，纳米载体无法通过血脑屏障，从而达到仅激动外周阿片受体的作用。法国学者开发出一种装载了亮氨酸脑啡肽 (leu-enkephalin, LENK) 的纳米药物，在动物模型中，该药成功的被血脑屏障阻隔，通过外周阿片受体实现炎症部位的长效止痛。另外，有学者设计出仅在特定 pH 环境中起作用的阿片受体激动剂，而炎性组织一般为酸性环境。该类药物以NFEPP 为代表，NFEPP 是基于芬太尼所设计的一种氟化衍生物。相比于芬太尼，该药不仅无法跨越血-脑屏障，氟原子的修饰作用还使其只有在酸性条件下才能与外周 μ 阿片受体结合，对呈现酸性微环境的病变组织实现靶向治疗。在结肠炎小鼠模型中，该药能够精准靶向炎症组织，有效缓解结肠疼痛，且完全不诱发成瘾、镇静、便秘等阿片样副作用。此外，研究人员基于 L-脑啡肽和角鲨烯的生物缀合物所开发的一种纳米载体镇痛药，通过制剂手段同样达到了不入脑而仅激活外周阿片受体的目的。 04 改变中枢分布动力学的阿片受体激动剂有假说认为 μ 受体激动剂的成瘾作用与其进入中枢的速度有关，但镇痛效果只与中枢暴露水平有关，那么开发以较低速率穿过血脑屏障的新型阿片受体激动剂，有可能降低成瘾。NKTR-181是一种聚合物-药物偶联物，通过聚乙二醇侧链 (polyethylene glycol, PEG) 来降低 μ 阿片类激动剂穿过血脑屏障的速度，在降低阿片类镇痛药成瘾性和滥用的同时，并具有显著的镇痛效力。目前，在腰痛和慢性非癌性痛病人中完成 3 期临床试验，其治疗相关不良反应 (TEAEs) 发生率为72%，最常见的不良反应为便秘 (26%)，恶心 (12%)。遗憾的是，目前美国 FDA 并没有通过 NKTR-181的上市申请。 05 内源性阿片肽降解酶抑制剂内源性阿片肽存在于与疼痛相关的中枢、外周神经系统以及外周损伤组织中。试验表明在炎性痛和神经病理性疼痛的动物模型中，通过抑制内源性阿片肽降解酶，可以增加疼痛相关部位内源性阿片肽的水平，达到镇痛作用。研究较多的是双重脑啡肽降解酶抑制剂 DENK，同时具有抑制氨基肽酶 N (aminopeptidase N, APN)和中性肽链内切酶 (neutral endopeptidase, NEP) 的作用。机体接受疼痛刺激时，会内生出脑啡肽，以达到“生理性”镇痛。DENK抑制剂通过在有大量脑啡肽及其降解酶的地方发挥作用，放大“生理性”镇痛，具有一定意义上的定向作用。与吗啡不同的是，在啮齿动物中给予高剂量 DENK 抑制剂，不会导致耐受、镇静、呼吸抑制、呕吐、便秘或依赖。DENK 是一类药物的总称，其中，PL265 可缓解啮齿动物角膜炎所致的眼痛和炎症，目前已进入临床试验阶段。 06 抑制阿片类药物成瘾作用的新靶点研究者对线虫基因的900多种突变进行测试，以观察是否导致对阿片类药物敏感性的变化，发现 FRPR-13 基因可能有意义。同时，在哺乳动物中也发现了 FRPR-13 的同源基因，该基因编码 GPR139 蛋白。在小鼠中，GPR139 与μ受体共表达，可抑制G蛋白耦联受体信号转导。缺失 GPR139 的小鼠对吗啡诱导的奖赏和镇痛的敏感性增加。当研究人员给小鼠服用激活 GPR139 的药物时，小鼠表现出更加依赖阿片类药物；相反，抑制、消除 GPR139 则增强了阿片类药物的止痛效果。因此， GPR139 可能是提高阿片类药物安全性的有效靶点。参考资料 [1]吴鸽,林沈娴,朱奇,等.阿片类药物是否穷途末路？[J].中国疼痛医学杂志,2021,27(03):212-215. [2]贺春波,王丹,杨淑佳,等.新型阿片类镇痛药的研发进展[J].中国药房,2024,35(17):2176-2180. END 【生物制药新锐说直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

2022-03-15

·BioSpace

Nektar Left Reassessing After Canceled Melanoma Trials

Smith Collection/Gado/Getty Images After the announcement, Nektar shares dropped 36%, going from $6.47 per share to $4.16. Smith Collection/Gado/Getty Shares of Nektar Therapeutics plunged after a disappointing clinical announcement on Monday. This has prompted the cancellation of two trials and left the company scrambling to find solutions. Nektar and Bristol Myers Squibb announced data from their joint Phase III PIVOT IO-001 study, which was testing Nektar’s immunotherapy drug bempegaldesleukin in combination with BMS’s Opdivo (nivolumab) compared with Opdivo alone to treat unresectable or metastatic melanoma. Unfortunately, the study did not meet its primary endpoints. The results were so dismal that BMS and Nektar not only canceled the PIVOT IO-001 study, they also discontinued their PIVOT-12 study, another Phase III trial where the partners were evaluating the same drugs but for adjuvant melanoma. The announcement is undeniably more difficult for Nektar. BMS had significant revenues of more than $46 billion in 2021, and has a diverse pipeline of products. However, Nektar, which focuses on oncology and immunology diseases, only brought in $101.9 million in revenue last year. After the announcement, Nektar stocks plunged 36%, dropping from $6.47 per share to $4.16. The collaboration with BMS had been a deal worth over $1 billion when the partnership was started in 2018. This was also just the latest in several tough announcements Nektar has had to make. When the company shared its Q4/full-year 2021 financial report just a few weeks ago, Nektar had a year net loss of $523.8 million. Its 2021 revenue was also around $50 million lower than it was in 2020, “due to the recognition of $50.0 million in total milestones from Bristol-Myers Squibb for the initiation of registrational trials of bempegaldesleukin plus Opdivo® in adjuvant melanoma,” the press release noted. Even before this, Nektar was struggling. In May 2019 , the company created a new subsidiary called Inheris Biopharma to commercialize a new opioid product, NKTR-181. In January 2020 , the U.S. Food and Drug Administration voted unanimously 27-0 to not approve the drug. The move dropped shares of Nektar by 14.5% and forced the company to eat $45.2 million in impairment charges. Still, there’s light at the end of the tunnel. Nektar has a few other products that, if successful, could keep the company afloat. NKTR-255 is currently in Phase I/II testing for blood cancers and solid tumors, while NKTR-358 is being tested in patients with lupus, ulcerative colitis and atopic dermatitis in a collaboration with Eli Lilly . Nektar is also partnering with Merck on a late-stage head and neck cancer study . These partnerships have already garnered Nektar around $800 million. If they prove successful, the alliances could help overcome this loss. Nektar also expects to announce top-line data in two more studies with its bempegaldesleukin drug in renal cell carcinoma and bladder cancer within the next few weeks. In the meantime, Nektar is scrambling to prop up the worth of its stocks with a restructure. “Today’s results will obviously mean that we have to make changes to our business operations and the structure of Nektar,” said Nektar CEO Howard Robin. “These changes will be substantial and will be difficult to undertake, but we’re preparing a plan that has a goal of establishing a minimum cash runway through the end of at least 2024 with our existing cash balance.”

临床3期财报临床失败

2021-01-06

·Endpoints

After an up-and-down year, Nektar watches development head Wei Lin walk away as it pursues pipeline rebound

More than any other year in recent memory, 2020 was a rollercoaster of highs and lows —mostly lows. Just ask San Francisco’s Nektar: Despite ditching its opioid program in January and offloading royalties to its two US-marketed meds, the biotech still has hopes for its pipeline to hit a rebound this year. But that rebound won’t happen under the watch of senior VP and head of development Wei Lin, who is stepping down and leaving immunology head Brian Kotzin to step in. Lin is “leaving the company to pursue another opportunity,” Nektar announced on Wednesday. It’s unclear where the Genentech vet is headed next. Nektar poached Lin from Genentech in 2018, where he held roles such as global development leader for cancer immunotherapy and senior medical director over a seven-year stint. The Harvard Medical School grad joined Nektar as senior VP and head of oncology before getting promoted to head of development. “Over the past two years, Wei has played a leadership role in recruiting an experienced clinical development organization and executing a late-stage clinical development strategy for BEMPEG, positioning it for future success,” chief R&D officer Jonathan Zalevsky said in a statement. “I would like to thank him for his contributions to Nektar, and wish him the best in his next opportunity.” With big shoes to fill, Kotzin is stepping up as interim CMO and head of development. The Amgen vet joined Nektar in 2017 and helped lead early development of NKTR-255, the company’s IL-15 receptor agonist currently in two Phase II studies: one for non-Hodgkin’s lymphoma and multiple myeloma in combo with Rituxan or Darzalex, and another in head, neck and colorectal cancer paired with Erbitux. He also spearheaded the Eli Lilly-partnered NKTR-358 program, which is in Phase II for systemic lupus erythematosus and Phase Ib studies for psoriasis and atopic dermatitis. At Amgen, Kotzin served as VP of global clinical development and head of inflammation therapeutics, as well as VP of translational sciences and head of medical sciences/early development. “This is an exciting time for the company with multiple registrational studies underway in a range of tumor types for BEMPEG, a broadening clinical program for NKTR-358 in a number of auto-immune disorders, and an emerging opportunity for NKTR-255 in both hematological malignancies and solid tumors,” Kotzin said. Last month, Nektar sold the royalties to Adynovate and Movantik off to Healthcare Royalty Management for $150 million in cash. The biotech said it would funnel most of the money into two programs: bempegaldesleukin (or NKTR-214) and NKTR-255. Bempegaldesleukin, Nektar’s lead program, is being studied in several Phase III trials in combination with Bristol Myers Squibb’s Opdivo. The CD122-preferential IL-2 agonist is being evaluated in several indications, including metastatic melanoma, renal cell carcinoma and muscle-invasive bladder cancer. That news came just less than a year after Nektar dropped its opioid program, NKTR-181, which was rebuffed by an FDA adcomm last January. The panel voted 27-0 against approving the drug, citing concerns that patients could abuse it and causing their stock $NKTR to fall 15%. On Wednesday morning, the company’s stock was down 0.61%, at $17.97 a share.

免疫疗法合作

100 项与 Loxicodegol 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14146

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
背痛	申请上市	美国	Nektar Therapeutics	-
慢性疼痛	临床3期	美国	Nektar Therapeutics	2015-03-11
腰痛	临床3期	美国	Nektar Therapeutics	2015-03-11
膝关节炎	临床2期	美国	Nektar Therapeutics	2012-06-01
肌肉骨骼疼痛	临床2期	美国	Nektar Therapeutics	-

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01619839 (CTgov)	临床2期	慢性疼痛 \| 膝关节炎	296	Placebo (Placebo)	憲選夢襯餘範鹹淵淵顧(夢網壓糧衊醖鏇積膚鬱) = 網夢壓艱願衊觸鬱餘憲鹹範鬱鹹觸夢範觸鏇醖 (膚獵製衊構構淵淵觸憲, 0.168) 更多	-	2021-08-02
				NKTR-181 (100 mg NKTR-181)	選鑰憲顧鏇獵築鑰窪淵(鬱鬱窪觸醖鏇願範網積) = 獵淵夢鹹築襯餘廠顧憲選鏇餘觸夢醖餘構積窪 (齋顧築獵蓋蓋構齋醖願, 鑰積鹽蓋艱鹽衊積鏇築 ~ 淵繭積齋觸艱蓋淵繭鏇) 更多
NCT03802227 (CTgov)	临床1期	慢性疼痛	8	placebo+oxycodone+NKTR-181 (NKTR-181)	製艱範鏇鬱廠糧憲觸簾(淵鏇醖願衊鏇夢壓廠願) = 憲繭蓋鏇蓋糧遞襯遞選艱遞夢餘顧襯壓醖願築 (齋鏇選襯醖鏇醖襯鹹艱, 0.12) 更多	-	2021-05-27
				Oxycodone (Oxycodone IR 40 mg)	製艱範鏇鬱廠糧憲觸簾(淵鏇醖願衊鏇夢壓廠願) = 簾選膚鹽遞願壓網遞衊艱遞夢餘顧襯壓醖願築 (齋鏇選襯醖鏇醖襯鹹艱, 0.34) 更多
NCT02362672 (SUMMIT-07, CTgov)	临床3期	腰痛 \| 慢性疼痛	1,189	NKTR-181 (NKTR-181)	願糧齋夢衊窪衊觸夢鹽(醖膚憲淵選積糧憲膚鏇) = 鏇鬱製願窪膚簾築繭憲齋鏇鹹繭廠壓鹽衊遞範 (構廠顧選齋築製繭鬱鏇, 0.11) 更多	-	2020-09-16
				Placebo to match NKTR-181 BID tablets (Placebo)	願糧齋夢衊窪衊觸夢鹽(醖膚憲淵選積糧憲膚鏇) = 製廠鬱餘鹽鑰顧夢鬱顧齋鏇鹹繭廠壓鹽衊遞範 (構廠顧選齋築製繭鬱鏇, 0.11) 更多
NCT02362672 (SUMMIT-07, Pubmed) 人工标引	临床3期	腰痛	610	NKTR-181	鹽餘鏇廠壓衊醖壓窪齋(願鹽構簾築簾醖構淵淵) = 網網簾鏇鏇選製糧壓廠鑰糧繭選築鬱積積憲艱 (窪壓願鬱製衊蓋鑰築鑰 ) 更多	积极	2019-06-01
				Placebo	鹽餘鏇廠壓衊醖壓窪齋(願鹽構簾築簾醖構淵淵) = 憲憲淵憲夢衊齋鹽糧糧鑰糧繭選築鬱積積憲艱 (窪壓願鬱製衊蓋鑰築鑰 ) 更多